Nanofabricated sequencing devices with deterministic membrane apertures bordered by electromagnetic field enhancement antennas

Abstract

The invention is notably directed to an optical sensing device (1, 1a). The device has a layer structure comprising a substrate (10), a dielectric layer (11), and opposite antenna elements (17). The substrate is structured to laterally delimit a cavity. The dielectric layer extends on top of the substrate and forms a membrane spanning the cavity. The membrane including n apertures (i.e., nanopores) to the cavity, where n≥1. Two or more apertures (30) are preferably provided (n≥2). More preferably, the number of apertures is larger than or equal to 100 or, even, 400. There are n pairs of opposite antenna elements, which are patterned on top of the dielectric layer, on opposite lateral sides of respective ones of the n apertures. The n pairs of opposite antenna elements define n respective gaps extending between opposite antenna elements of the n pairs along respective directions parallel to a main plane of the substrate. The n pairs of opposite antenna elements define, together with the respective apertures, n molecular passages. Each passage extends from the cavity through a respective one of the n apertures (i.e., through the membrane) and a respective one of the n gaps, along a direction transverse to the main plane of the substrate. The average length of the n gaps along said respective directions is between 4 nm and 20 nm. The n gaps define respective electromagnetic field enhancement regions, in which electromagnetic radiation can be concentrated upon irradiating the antenna elements, for optically sensing molecules, in operation. Moreover, the average diameter of the n apertures is larger than or equal to the average length of the gaps along their respective directions. Thus, the minimal cross-sectional dimension of each of the n passages is limited by a respective one of the n gaps along said respective directions. The invention is further directed to related apparatuses, sensing methods, and fabrication methods.

1 . An optical sensing device having a layer structure comprising:
 a substrate structured to laterally delimit a cavity;   a dielectric layer, which extends on top of the substrate and forms a membrane spanning the cavity, the membrane including n apertures to the cavity, where n≥1; and   n pairs of opposite antenna elements, which are patterned on top of the dielectric layer, on opposite lateral sides of respective ones of the n apertures, and define n respective gaps extending between opposite antenna elements of the n pairs along respective directions parallel to a main plane of the substrate, so as to define n molecular passages, each extending from the cavity through a respective one of the n apertures and a respective one of the n gaps along a direction transverse to the main plane of the substrate,   
       wherein,
 an average length of the n gaps along said respective directions is between 4 nm and 20 nm, whereby the n gaps define respective electromagnetic field enhancement regions, in which electromagnetic radiation can be concentrated upon irradiating the antenna elements, for optically sensing molecules, in operation, and 
 an average diameter of the n apertures is larger than or equal to said average length of the gaps along said respective directions, whereby a minimal cross-sectional dimension of each of the n molecular passages is limited by a respective one of the n gaps along said respective directions. 
 
     
     
         2 . The optical sensing device according to  claim 1 , wherein
 the number n of the apertures is larger than or equal to 100.   
     
     
         3 . The optical sensing device according to  claim 2 , wherein
 the average diameter of the n apertures is equal to the average length of the gaps, subject to ±2 nm, whereby inner ends of the antenna elements of each of the n pairs are substantially flush with inner walls of the respective n apertures in the membrane.   
     
     
         4 . The optical sensing device according to  claim 2 , wherein
 the diameters of the apertures and the lengths of the gaps are essentially constant, subject to a dispersion of less than 2 nm.   
     
     
         5 . The optical sensing device according to  claim 2 , wherein
 an average, in-plane separation distance between the apertures is between 1 and 10 microns.   
     
     
         6 . The optical sensing device according to  claim 1 , wherein
 said dielectric layer is a first dielectric layer,   the optical sensing device includes a second dielectric layer,   the substrate is on top of the second dielectric layer, and   the substrate and the second dielectric layer are jointly structured to form a recess delimiting said cavity.   
     
     
         7 . The optical sensing device according to  claim 6 , wherein
 the substrate comprises silicon,   each of the two dielectric layers comprises Si 3 N 4 , and   each of the antenna elements essentially comprises Au.   
     
     
         8 . The optical sensing device according to  claim 6 , further comprising
 one or more pairs of electrodes, wherein the electrodes of each of the pairs are on opposite sides of the first dielectric layer.   
     
     
         9 . An optical sensing apparatus, wherein the optical sensing apparatus comprises
 an optical sensing device according to  claim 1 ,   a distributed electromagnetic source configured to irradiate the antenna elements of each of the n pairs of opposite antenna elements, so as to concentrate electromagnetic radiation in the respective electromagnetic field enhancement regions, for optically sensing molecules in the respective gaps, and   a detector configured to optically detect optical signals as modulated and/or generated by the molecules in said regions, in operation.   
     
     
         10 . The optical sensing apparatus according to  claim 9 , wherein
 the optical sensing apparatus further comprises an electrical circuit comprising one or more pairs of electrodes, wherein the electrodes of each of the pairs are on opposite sides of the first dielectric layer, the electrical circuit configured to apply a voltage bias between electrodes of each of the pairs to urge molecules through the molecular passages.   
     
     
         11 . A method of fabrication of an optical sensing device according to  claim 1 , wherein the method comprises
 providing a substrate;   depositing a dielectric layer on top of the substrate;   patterning fiducial marks on both the dielectric layer and the substrate;   patterning n pairs of opposite antenna elements on top of the dielectric layer, based on an alignment protocol exploiting the fiducial marks patterned, so as to define n respective gaps extending between opposite antenna elements of respective ones of the n pairs along respective directions parallel to a main plane of the substrate, wherein n≥1, and an average length of the n gaps along said respective directions is between 4 nm and 20 nm;   depositing a protective layer, for it to coat inner ends of the opposite antenna elements of each of the n pairs;   dry etching the dielectric layer at locations defined according to the fiducial marks, to open n apertures through the dielectric layer, between opposite antenna elements of respective ones of the n pairs, for the opposite antenna elements of the n pairs to be on opposite lateral sides of respective ones of the n apertures;   coating the opposite antenna elements of the n pairs of opposite antenna elements and the dielectric layer with a protective polymer, for it to plug the n gaps and the n apertures;   structuring the substrate to form a recess extending up to the dielectric layer, so as for the latter to extend on top of residual, peripheral portions of the substrate and form a membrane spanning a cavity delimited by the recess, and   removing the protective polymer, to free up n molecular passages, each extending from the cavity through a respective one of the n apertures and a respective one of the n gaps along a direction transverse to the main plane of the substrate, to obtain an optical sensing device, in which
 the n gaps define respective electromagnetic field enhancement regions, in which electromagnetic radiation can be concentrated upon irradiating the antenna elements, for optically sensing molecules, in operation of the optical sensing device, and 
 an average diameter of the n apertures is larger than or equal to said average length of the gaps along said respective directions, whereby a minimal cross-sectional dimension of each of the n molecular passages is limited by a respective one of the n gaps along said respective directions. 
   
     
     
         12 . The method according to  claim 11 , wherein
 the dielectric layer is a first dielectric layer; and   the method further comprises
 depositing a second dielectric layer below the substrate; and 
 after patterning the fiducial marks and prior to patterning the n pairs of opposite antenna elements, patterning the second dielectric layer, so as for residual, peripheral portions of the second dielectric layer to delimit the recess to be formed next. 
   
     
     
         13 . The method according to  claim 11 , wherein
 the fiducial marks are patterned using electron beam lithography and a dry etching procedure.   
     
     
         14 . The method according to  claim 13 , wherein
 the fiducial marks are patterned as slits extending through the dielectric layer and partly in the substrate.   
     
     
         15 . The method according to  claim 14 , wherein the n pairs of opposite antenna elements are patterned by:
 depositing a photoresist on top of the dielectric layer, for the photoresist to plug the slits;   structuring the photoresist by photolithography, for it to form residual plugs at a level of the slits;   depositing a metallic layer on top of the dielectric layer and the residual plugs, and removing the residual plugs to define openings at the level of the slits;   depositing an electron beam resist on top of the metallic layer and structuring the electron beam resist by electron beam lithography in accordance with shapes of the antenna elements; and   etching the metallic layer through the structured electron beam resist using ion beam etching, to obtain the antenna elements.   
     
     
         16 . The method according to  claim 11 , wherein
 the protective layer is an alumina layer, which is obtained by
 coating an electron beam resist, 
 opening cavities at the level of the gaps, and 
 depositing the protective layer by atomic layer deposition at a temperature that is less than 90 C, for it to notably coat the inner ends of the opposite antenna elements of each of the n pairs. 
   
     
     
         17 . The method according to  claim 11 , wherein
 the substrate essentially comprises silicon, each of the two dielectric layers essentially comprises Si 3 N 4 , and each of the antenna elements essentially comprises Au.   
     
     
         18 . A method for optically sensing an analyte, the method comprising:
 providing an optical sensing device having a layer structure comprising:
 a substrate structured to laterally delimit a cavity; 
 a dielectric layer, which extends on top of the substrate and forms a membrane spanning the cavity, the membrane including n apertures to the cavity, where n≥1; and 
 n pairs of opposite antenna elements, which are patterned on top of the dielectric layer, on opposite lateral sides of respective ones of the n apertures, and define n respective gaps extending between opposite antenna elements of the n pairs along respective directions parallel to a main plane of the substrate, so as to define n molecular passages, each extending from the cavity through a respective one of the n apertures and a respective one of the n gaps along a direction transverse to the main plane of the substrate, wherein, 
 an average length of the n gaps along said respective directions is between 4 nm and 20 nm, whereby the n gaps define respective electromagnetic field enhancement regions, in which electromagnetic radiation can be concentrated upon irradiating the antenna elements, for optically sensing molecules, in operation, and 
 an average diameter of the n apertures is larger than or equal to said average length of the gaps along said respective directions, whereby a minimal cross-sectional dimension of each of the n molecular passages is limited by a respective one of the n gaps along said respective directions, 
   irradiating the pairs of antenna elements of the optical sensing device, to concentrate electromagnetic radiation in the electromagnetic field enhancement regions, and   sensing molecules in the n gaps by optically detecting optical signals that are modulated and/or generated by the molecules in the n gaps, thanks to an optical detector.   
     
     
         19 . The method according to  claim 18 , wherein the method further comprises
 applying an electric field across the membrane to urge molecules to the molecular passages and trap the molecules at the respective gaps, by virtue of a combined effect of the electric field applied and the electromagnetic radiation concentrated in the respective electromagnetic field enhancement regions.   
     
     
         20 . The method according to  claim 18 , wherein the method further comprises:
 jointly controlling the applied electric field and an intensity at which the pairs of antenna elements are irradiated to control a progression of the molecules through the n molecular passages, while optically detecting the optical signals.   
     
     
         21 - 22 . (canceled)